Method and composition for prevention and treatment of oral disease

ABSTRACT

The use of stabilized chlorine dioxide as a composition for the treatment and prevention of oral disease and the reduction of oral malodor is disclosed. Chlorine dioxide is an effective anti-plaque agent, anti-gingivitis and anti-periodontitis agent, and also effective to destroy malodorous sulfur compounds. Preferred concentrations are in the range of 0.005% to 2% and the chlorine dioxide may be in the form of a wash or rinse in solution, a soak or as a toothpaste.

This is a continuation of application Ser. No. 017,241, filed Dec. 29,1986, now U.S. Pat. No. 4,696,811, which is a continuation ofapplication Ser. No. 846,342, filed Mar. 31, 1986, now abandoned whichis a continuation of application Ser. No. 636,027, filed Jul. 30, 1984,now abandoned, and the present application is a continuation ofapplication Ser. No. 947,079, filed Dec. 26, 1986, now U.S. Pat. No.4,689,215, which is a continuation of application Ser. No. 846,342, Mar.31, 1986, now abandoned, which is a continuation of application Ser. No.636,027, filed Jul. 30, 1984, now abandoned; all of the above referencedprior applications name as inventor the same inventor as the presentapplication.

The present invention relates to a method and composition for theprevention and treatment of oral disease and reduction of mouth odors.More particularly, the present invention relates to the use ofstabilized chlorine dioxide for the prevention and treatment of oraldisease and reduction of mouth odors.

The volatile sulfur compounds, hydrogen sulfide (H₂ S) methylmercaptan(CH₃ SH) and di-methylmercaptan (CH₃)₂ S are recognized in the currentdental literature as being the major contributors to oral malodor.Numerous researchers using organoleptic, chemical, amperometric, massspectrometric, or gas liquid chromatographic methods have demonstratedthat these volatile sulfur compounds are present in the head space andvapor of purified saliva and in individual samples of mouth air. In mostpersons, hydrogen sulfide and methylmercaptan constitute over 90% of thetotal volatile sulfur content identified in mouth air.

These malodorous volatile sulfur compounds are generated primarilythrough the putrifactive action of oral microorganisms on sulfurcontaining amino acids, peptones or proteins found in the mouth. Thesesubstrates are readily available in saliva and dental plaque or may bederived from proteinaceous food particles trapped between the teeth, inthe gingival crevice or adhering to the mucous membranes and theirregular surface of the tongue as well as exfoliated oral epithelium,food debris and the like. Current studies have indicated that mouth odornot only comes from the posterior dorsal surface of the tongue but alsofrom periodontal pockets. People with periodontal involvement have anattendant increase in oral malodor from disintegrated epithelial cells.

It is commonly accepted that the etiology of both smooth surface dentalcaries and periodontal disease is directly associated with theaccumulation on teeth of bacterial plaque. Dental plaque is formed by acombination of events starting with a salivary proteanaceous coating ofthe tooth and the subsequent adhesion to the coating (pellicle) bystreptococcus forms. Dextrans produced by bacteria, principally S.mutans and S. sanguis, are produced from sucrose and with the assistanceof bacterially produced glucosyltransferases convert sucrose intoglucose and fructose and ultimately the glucose into dextrans. Thedextrans act as a nutrient substrate for the growth of additionalorganisms and the production of acids which demineralize both enamel anddentin causing decay. Other strains of alpha streptococci andlactobacillus organisms include but are not limited to S. sanguis, S.mitis and S. salivarius.

Gingivitis, adult and juvenile forms of periodontists and acutenecrotizing ulerative gingivitis and other periodotopathies are known tobe caused by bacteria. Gingivitis occurs from coronol dental plaque andperiodontitis by the infection extending into the periodental pocket orspace between the gingiva and the tooth root.

Various substances have been tested for their ability to disrupt plaqueor prevent its formation and to treat mouth odor such as antibiotics,chlorhexdines, oxine, and alexidine.

The prior art compositions that have been used and tested have foundsome acceptance but are generally of limited efficacy in reducing orpreventing dental caries and periodontitis, gingivitis, plaqueaccumulation and mouth malodor. Accordingly, there exists a clear needfor a composition which will effectively inhibit or control theformation of bacterial plaque and suppress organisms such as but notlimited to (1) S. mutans, which is implicated as the major cause ofhuman dental decay; (2) Bacteroides gingivalis, an Actinobacillusactinomycetumcomitans which is implicated in human periodontitis; and(3) will reduce odor intensity in the mouth through the control ofhydrogen sulfide and methylmercaptan.

Broadly, the present invention contemplates the use of stabilizedchlorine dioxide for the treatment of the mouth as a deodorizing agent,anti-plaque agent, bacteriacide for treatment of gingivitis and as abactericidal fungicidal and viralcidal agent in other relatedapplications.

The term stabilized chlorine dioxide is a term well used in the industryand those skilled in the art will and do appreciate the various forms orcompositions thereof which are available to perform certain intendedfunctions and purposes. Furthermore, U.S. Pat. No. 3,271,242 describes aform of stabilized chlorine dioxide and a method of making same which isparticularly useful in carrying out the present invention. Because thecompound termed stabilized chlorine dioxide is well known to thoseskilled in the art, such knowledge permits the selection of a particularembodiment of such compound for specified purposes, as evidenced bypages 139 to 140 of a book entitled Chlorine Dioxide by W. J.Masschelein published by the Ann Arbor Science Publishers, Inc.,copyright 1979; note also footnotes 112 to 116 cited therein which are:112. Schirle, C. "Bull Inst. Text. Fr. 41: 21 (1953); 113. Haller, R."Textil-Rundschau" 7: 359 (1952); 114. Das. D. B., and J. B. Speakman"J. Soc. Dyers Colurists" 66: 583 (1950); 115. German Pat. No. 1,027,629(1958); "Chem, Abst. "54: 14712 (1960); 116. Tumanova, T. Z. "Bum.Prom." 6: 7 (1968); "Chem. Abstr." 69: 445522 (1968). A form ofstabilized chlorine dioxide usable with the present invention is soldunder the trademark "PUROGENE" by Oxyfresh USA, Inc. It is to be notedthat Purogene may be purchased from any Service Center of the Searsdepartment stores.

Chlorine dioxide is quite soluble and is widely used as an industrialpurification and oxidizing agent in such areas as manufacture of woodpulp, water treatment and similar applications due to its bactericidal,disinfectant, and sterilization qualities. In the present invention acomposition containing stabilized chlorine dioxide may be used fortreatment of the mouth either in a solution, for example, as a mouthwashor in a toothpaste generally in concentrations of below approximately0.2% for the control of odorgenic microorganisms, bacterial plaque,gingivitis and bacteria which cause these conditions. Similarly,chlorine dioxide is also effective as a cellular debridement agentfollowing surgical procedures, sanitizer denture soak and contact lenssoaking agent.

The use of chlorine dioxide and its effect on man has been clinicallyevaluated. The relative safety of oral injection of chlorine dioxide wasdemonstrated extensively in animals and later in humans by Lubbers,Chauan, and Bianchine, Environmental Health Perspectives, Volume 46,Pages 57-62, 1982.

EXAMPLE I Deodorizing Mouthwash

In an effort to find a suitable control agent for mouth odor, attentionwas directed towards the use of chlorine dioxide. The characteristics ofchlorine dioxide which make it especially useful is that it isantiseptic, a bactericide, generally colorless, odorless, highly stableand has no apparent deterimental or deliterious effect on humans atconcentrations involved. As pointed out above, mouth malodor isprimarily caused by volatile sulfur compounds, hydrogen sulfidemethylmercaptan and dimethyl mercaptan. These chemicals are produced asdegradation products of microorganisms acting on exogenous andendogenous proteinaceous substrates, oral epithelium, food debris andsaliva. In order to control mouth odor, a deodorizing mouth washconsisting of a solution of 0.02% chlorine dioxide in deionized waterwas utilized as a rinse. Evidence indicates efficacy at lesser dilutionsto 0.005% with more rapid effect at dilutions to 0.2%. Sulfides arereadily oxidized by chlorine dioxide. Bacteria implicated in theproduction of malodor were also effectively controlled. Inhibition ofthese microorganisms will reduce dental plaque.

The chlorine dioxide mouthwash or rinse solution serves to attackproduction and origin of malodor from the mouth by splitting the sulfidebonds of both hydrogen sulfide and methylmercaptan. Therefore, deliveryof stabilized chlorine dioxide provides reduction and elimination ofthese odors. Further, the bacteriostatic, bactericidal, fungistatic andfungicidal activity of stabilized chlorine dioxide will reduce thenumber of microorganisms which assist in the production of oral debrisleading to disintegration or organic compounds and ultimately producinghydrogen sulfide and methylmercaptan. The known organisms includestaphlococci, B. subtilis, B. pyrocaneus, Colon bacilli, B.melanogenicus, Clostridia, B. sporogenes, B. histolyticum, and T.mucosum.

The mouthwash may be delivered as a simple rinse which bathes thetongue. Literature indicates that over 50% of mouth odor originates onthe mouth and tongue surface, particularly the posterior dorsal surfaceof the tongue. Accordingly, a rinse is an effective treatment. However,persons with periodontal involvement may have an increase in oralmalodor from disintegrated epithelial cells. A mouth rinse will notpenetrate to attack gingival crevicular odorizers. Thus, to optimizetreatment with a mouthwash containing chlorine dioxide, the wash must bedelivered into the periodontal pockets as well as dorsal and lingualsurfaces. To accomplish this, the preferred treatment is achieved byinserting the delivery tip of a syringe into the pockets or gingivalcrevices or by administering the wash by a mechanically powered waterirrigating device such as those of the type sold under the trademark"Water Pik", manufactured by Teledyne Corp. Following irrigation, theuser can swish the wash throughout the mouth, covering the dorsalsurface of the tongue and other areas.

To improve the taste and appearance of the chlorine dioxide solution,appropriate sweeteners and colorings such as saccharin, pepperment andFTC #3 coloring agent may be added as is common with commerciallyavailable mouthwashes and is well-known to those in the art.

EVALUATION OF MOUTHWASH CONTAINING CHLORINE DIOXIDE FOR ITS EFFECT ONVOLATILE SULFUR COMPOUNDS

The test mouthwash which had a concentration of 0.5%, was dispersed in1/4 oz. aliquots in individual plastic containers. The study wasperformed over a 3-hour period on six human subjects with objectionableearly morning concentrations of volatile sulfur compounds (VSC) greaterthan 0.5 ng CH₃ SH/10 ml mouth air.

Rinsing Procedure: Following initial early morning VSC analysis on theday of evaluation, subjects were instructed to rinse, with vigorousswishing of rinse between teeth, for 30 seconds with 3/8 oz volumes ofthe test mouthwash. After the rinse was expectorated, the mouth wasrinsed for 30 seconds with 15 ml of 18 megavolt pure water.

VSC Analysis: All G.C. analysis were performed in duplicate on eachsubject at the following times:

1. Initial screening to select subjects with objectionable early morningconcentrations of VSC.

2. On the day of evaluation, analysis were performed on early morningmouth air samples before rinsing. These values served as controls. Thus,each subject served as his own control against which the effect of therinse was calculated. Immediately following these analysis, the subjectsrinsed and were re-analyzed, 3 min., 13 min., one hour, two hours and 3hours post-rinsing. The results are sumarized on the following table:

                                      TABLE 8                                     __________________________________________________________________________    SUMMARY MOUTH AIR VSC REDUCTION                                               Early Morning    One Hour         Two Hour        Three Hour                  Subject                                                                           H.sub.2 S*                                                                        CH.sub.3 SH*                                                                       H.sub.2 S*                                                                        % Red                                                                             CH.sub.3 SH*                                                                       % Red                                                                             H.sub.2 S*                                                                        % Red                                                                             CH.sub.3 SH*                                                                       % Red                                                                             H.sub.2 S*                                                                       % Red                                                                             CH.sub.3 SH*                                                                        %                 __________________________________________________________________________                                                               Red                OF. 1                                                                             0.82                                                                              0.72 0.39                                                                              52.44                                                                             0.37 48.61                                                                             0.39                                                                              52.44                                                                             0.59 18.06                                                                             0.75                                                                              8.54                                                                             1.08 +50                OF. 2                                                                             1.30                                                                              1.04 0.29                                                                              77.69                                                                             0.17 83.65                                                                             0.41                                                                              68.46                                                                             0.24 76.92                                                                             0.45                                                                             65.38                                                                             0.23 72.88              OF. 3                                                                             0.98                                                                              0.77 0.77                                                                              21.43                                                                             0.57 25.97                                                                             0.69                                                                              29.59                                                                             0.52 32.47                                                                             0.82                                                                             16.33                                                                             0.62 19.48              OF. 4                                                                             0.73                                                                              1.04 0.39                                                                              46.58                                                                             0.2  75.00                                                                             0.37                                                                              49.32                                                                             0.31 70.19                                                                             0.47                                                                             35.62                                                                             0.46 55.76              OF. 5                                                                             1.56                                                                              0.88 0.58                                                                              62.82                                                                             0.41 53.41                                                                             0.75                                                                              51.92                                                                             0.40 54.55                                                                             0.86                                                                             44.87                                                                             0.80  9.09              OF. 6                                                                             1.12                                                                              1.41 0.40                                                                              64.29                                                                             0    100 0.41                                                                              63.39                                                                             0    100 0.55                                                                             50.89                                                                             0.43 69.50              Average          54.21    64.44   52.52    58.70  36.94    30.25              % Reduction                                                                   __________________________________________________________________________     *ng/10 ml volume of mouth air                                            

The effectiveness of chlorine dioxide was tested both in vivo and invitro and demonstrated that stabilized chlorine dioxide will kill at the99% level in ten seconds Streptococcus mutans the principle organismimplicated in the etiology of dental caries as well as other strains oforganisms as demonstrated by the following tests:

                  IN VITRO                                                        ______________________________________                                        THE BACTERICIDAL EFFECT OF ClO.sub.2 AGAINST                                  STREPTOCOCCUS MUTANS                                                          pH     200 ppm ClO.sub.2  SURVIVED                                            of     Treatment                        %                                     Medium Seconds   Organisms/0.2 ml                                                                           No. Organisms                                                                           Kill                                  ______________________________________                                        10      5        40,000       68        99.83                                        10        40,000       16        99.96                                        20        40,000       5         99.99                                 5       5        40,000       1336      99.66                                        10        40,000       98        99.76                                        20        40,000       101       99.75                                 1       5        29,600       *TNTC     0.0                                          10        29,600       125       99.58                                        20        29,600       70        99.76                                 6       5        29,600       *TNTC     0.0                                          10        29,600       *TNTC     0.0                                          20        29,600       122       99.59                                 6       5        9,400        744       92.1                                         10        9,400        176       98.1                                         20        9,400        44        99.5                                  2       5        9,400        1248      86.7                                         10        9,400        920       90.2                                         20        9,400        640       93.2                                  ______________________________________                                         *Too numerous to count.                                                  

    ______________________________________                                        THE BACTERICIDAL EFFECT OF ClO.sub.2 AGAINST                                  BACTEROIDES GINGIVALIS                                                        pH     200 ppm ClO.sub.2  SURVIVED                                            of     Treatment                        %                                     Medium Seconds   Organisms/0.2 ml                                                                           No. Organisms                                                                           Kill                                  ______________________________________                                        5.21    5        53           0         100                                          10        53           0         100                                          20        53           0         100                                   5.96    5        53           0         100                                          10        53           0         100                                          20        53           0         100                                   ______________________________________                                    

    ______________________________________                                        THE BACTERICIDAL EFFECT OF ClO.sub.2 AGAINST                                  BACTEROIDES MELANINOGENICUS                                                   pH     200 ppm ClO.sub.2  SURVIVED                                            of     Treatment                        %                                     Medium Seconds   Organisms/0.2 ml                                                                           No. Organisms                                                                           Kill                                  ______________________________________                                        5.3    5         100,000      100,000   0                                            10        100,000      100,000   0                                            20        100,000      5,000     95                                    6.15   5         100,000      50,000    50                                           10        100,000      50,000    50                                           20        100,000      0         100                                   4.97   5         100,000      100,000   0                                            10        100,000      100,000   0                                            20        100,000      3,300     97                                    5.86   5         100,000      50,000    50                                           10        100,000      50,000    50                                           20        100,000      0         100                                   4.99   10        10,000       10,000    0                                            20        10,000       0         100                                          30        10,000       0         100                                   6.29   10        10,000       5,000     50                                           20        10,000       0         100                                          30        10,000       0         100                                   4.97   10        10,000       10,000    0                                            20        10,000       0         100                                          30        10,000       0         100                                   5.85   10        10,000       3,000     70                                           20        10,000       0         100                                          30        10,000       0         100                                   ______________________________________                                    

    ______________________________________                                        THE BACTERICIDAL EFFECT OF ClO.sub.2 AGAINST                                  ACTINOBACILLUS ACTINOMYCETEMCOMITANS                                          pH     200 ppm ClO.sub.2  SURVIVED                                            of     Treatment                        %                                     Medium Seconds   Organisms/0.2 ml                                                                           No. Organisms                                                                           Kill                                  ______________________________________                                        4.97   5         8,560        *TNTC     0                                            10        8,560        312       96.3                                         20        8,560        67        99.2                                  5.87   5         8,560        *TNTC     0                                            10        8,560        2         99.9                                         20        8,560        1         99.9                                  ______________________________________                                         *Too numerous to count.                                                  

Materials and Methods

Materials used in all experiments:

1.0 AC 5215 Odorid, ClO₂ 1000 ppm, Biocide Chemical Co. Norman, OK

1.1 Chlorine-free distilled water employed throughout

1.2 Stirring apparatus, magnetic mixer with magnetic bar; IEC Centrifuge6000

1.3 Petri plates (12×50 mm, 15×100 mm)

1.4 HCl 0.1N, NaOH 0.1N

1.5 Sodium thiosulfate solution 15 l, employed 0.04 ml

1.6 Orthotolidine (o-toluidine) J T Baker, Baker Grade boiling point200°-201° C.; C₄ C₆ H₄ HN₂, Standard Methods for Examination of Waterand Wastewater, 14th Ed. 1975 Neutral Orthotolidine Reagent, 0.04 mlemployed

1.7 Diluent, saline with 0.5% Tween 80

Materials used in individual experiments:

1.0 Exp. Streptococcus mutans ATCC #27152

1.1 Brain Heart Infusion Broth employed for initial culture

1.2 Plate counts performed on plate count agar.

2.0 Exp. Bacteroides gingivalis ATCC #33277

2.1 Anaerobic Typtic Soy Agar (TSA) with 5% sheep blood employed forinitial isolation.

2.2 Plate counts were performed on anaerobic TSA with 5% horse serum

3.0 Exp. Bacteroides melaninogenicus ATCC #15930

3.1 Anaerobic TSA with 5% sheep blood was employed throughout

3.2 Extended time interval for stirring of organisms was 30 seconds

4.0 Exp. Actinobacillus actinomycetumocomitans ATCC #29522

4.1 Initial cultures prepared on chocolate agar

4.2 Plate counts were performed on anaerobic TSA without sheep blood

Methods

Initially each ATCC culture employed was grown on the media documentedunder each organism. After isolation, all cultures were maintained onappropriate media. The initial bacterial count was determined by platingten-fold serial dilutions of the selected organism in its respectivemedium. After incubation, the bacterial colonies were counted and 0.2 mlof the selected dilution was employed against ClO₂, ClO₂ was employed at200 ppm. 0.8 ml of ClO₂ was mixed with 0.2 ml of organisms suspensionand map-mixed for the selected length of time in seconds--5, 10, 20, and30. Two organism--ClO₂ mixtures were mixed by a 45° tilting rotation ina small tube for the selected period of time.

In each experiment, subsequent to each mixing time of ClO₂organism-mixtures, excess ClO₂ was neutralized by the addition of 0.04ml of sodium thiosulfate. To assure that complete neutralization ofexcess ClO₂ had occurred, 0.04 orthotolidine was added to each ClO₂-organism-sodium thiosulfate mixture. When C10₂ is neutralized, themixture remains clear. If residual ClO₂ is present, the mixture turnsyellow after the addition of orthotolidine. Additional controls todetermine the effect of each reagent singly or in combination againsteach organism include sodium thiosulfate-organism mixtures and sodiumthiosulfate orthotolidine organism mixtures. A control plate countwithout reagents was included for each organism.

All cultures except Streptococcus mutans were grown anaerobically in COat 37° C. for 48-96 hours. Streptococcus mutans was grown aerobically at37° C. for 48 hours.

IN VIVO CHLORINE DIOXIDE EVALUATION

Thirty-nine periodontal pockets in twenty-nine patients were examined bydark field and phase microscopy. The motility and density of bacteriawere evaluated from zero to three with zero being no activity and threevery active.

Of the thirty-nine teeth, thirty were molars, three were bicuspids andsix were in the anterior region. Pocket dept ranged from 4 to 12millimeters.

The patients were instructed to use a 0.1% chlorine dioxide solutiontwice daily. Four of the patients used chlorine dioxide as a mouth rinseand twenty-five used it as an irrigant with monoject 412 twelve ccsyringe.

The findings follow:

    __________________________________________________________________________    CLINICAL EFFECT OF .10 CHLORINE DIOXIDE                                                                          BEFORE                                                                             BEFORE                                                 BEFORE                                                                              AFTER       DARK DARK                                  TOOTH #                                                                             CODE #                                                                             SURFACE                                                                             PHASE PHASE                                                                              % CHANGE                                                                             FIELD                                                                              FIELD % CHANGE                        __________________________________________________________________________    14    001  M     2     0    100%   3     1+   50%                             23    001  D     +     0    100%   2    +     75%                             30    002  D     0     0     0%    1    0     100%                            18    003  D     2     0    100%    2+   1-   70%                             15    004  L     +     0    100%   +    +      0%                             18    004  D     2     0    100%    2+  1     60%                             14    005  M     2     1     50%   2    2      0%                             30    005  L     1     0    100%   2    0     100%                            15    006  L     0     0    0      2    0     100%                            19    007  D     0     0    0      3    0     100%                            31    008  B     2     0    100%    2+  0     100%                            7     009  D     3     0    100%   3    2     33%                             2     010  M     1     0    100%   2    0     100%                            4     011  M     0     0    0      2    0     100%                            15    011  D     1     0    100%   3     1-   75%                             3     012  M     2      1-   63%   3    2     33%                             14    012  M     2     1     50%   3    2     33%                             18    013  M     0     0    0      3    1     67%                             3     014  M     0     0    0      1    0     100%                            2     015  M     2     1     50%   3    2     33%                             2     015  D     2     +     75%   3    +     83%                             21    016  D     0     0    0       2+  0     100%                            14    017  M     1     0    100%   3    2     33%                             3     018  M     1     0    100%   1    0     100%                            32    019  D      1+   0    100%   2    0     100                             31    020  B     2     +     75%   3    +     83%                             2     021  M      2+   1     60%   3    2     33%                             32    022  D     1     0    100%   1    +     50%                             31    023  M     1     0    100%   3    0     100%                            3     024  D     2     0    100%   2    0     100%                            15    025  D     2     0    100%   3    1     67%                             26    025  D     0     0    0      3    1     67%                             4     026  M     2     0    100%    2+   1-   70%                             12    026  M     1     +     50%   3    +     83%                             8     027  B     1     0    100%   2    1     50%                             3     028  M     1     0    100%   3    1     67%                             31    029  M     1     +     50%   3     1+   50%                             11    030  D     +     0    100+   1    +     50%                             __________________________________________________________________________

EVALUATION DATA

Phase (Thirty Pockets with Activity)

    ______________________________________                                        Number of Pockets                                                                             % Resolution                                                                             % of Total                                         ______________________________________                                        21              100%       70%                                                2               75%        6.67%                                              1               63%        3.33%                                              1               60%        3.33%                                              5               50%        16.07%                                             ______________________________________                                    

Mean resolution (All bacterial activity stopped or was reduced).

Dark Field (Thirty-nine pockets with Activity)

    ______________________________________                                        Number of Pockets                                                                             % Resolution                                                                             % of Total                                         ______________________________________                                        14              100%       35.89%                                             3               83%        7.69%                                              2               75%        5.13%                                              2               70%        5.13%                                              4               67%        10.26%                                             1               60%        2.56%                                              5               50%        12.82%                                             6               33%        15.38%                                             ______________________________________                                    

(Two of the pockets exhibited no reduction in bacteria after the use ofChlorine Dioxide.)

EXAMPLE II Toothpaste

As demonstrated above, chlorine dioxide can be an effective agent onodor producing micoorganisms and enzymes. However, the effectiveness ofchlorine dioxide can be enhanced when included as an ingredient of atoothpaste. Toothpaste is more effective than a rinse for removingmalodor from the gums or gingiva. The action of the brush dislodges deadcells and putrescent debris from the gingival crevices as well as on thevarious mouth surfaces and on the tongue. The chlorine dioxide containedin the toothpaste acts as discussed above to prevent malodor and serveas a deodorizer by attacking hydrogen sulfide and methylmercaptan. Atypical toothpaste would have the following composition: Chlorinedioxide approximately 0.005% to 0.2%, detergent polishing agent; calciumcarbonate; flavoring, saccharin; pepperment; coloring agent. These otheringredients may vary and are the basic ingredients in many toothpastesas is well-known to those in the art. Other formulations includingchlorine dioxide as the active ingredient would work as well.

EXAMPLE III Anti-Plaque Agent

Dental plaque, as mentioned above, is formed by a combination of actionsbeginning with saliva coating the the tooth and a subsequent adhesion tothe coating by streptococcus bacterial forms. S. mutans degrade sucroseinto glucose or fructose which are then compounded into dextrans andlevans. The dextrans act as a nutrient substrate for the growth ofadditional organisms and the production of acids which demineralizetooth enamel and dentin causing tooth decay. As indicated in the testdata above, chlorine dioxide is lethal to Streptococcus mutans in vitroand materally reduces their numbers in vivo. Dental plaque formation isreduced when the microbial content of the mouth is reduced. Thus,chlorine dioxide is an effective anit-microbial agent which functions asa dental plaque retardant or preventative and as an anti-cariogenicagent. Preferred concentrations are in the range from 0.005% to 0.2% insolutions as for example, in de-ionized water with suitable coloring andflavorings for patient comfort.

EXAMPLE IV Anti-gingivitis, Anti-periodontitis and Gingival BleedingPreventative

Gingivitis and the various forms of periodontitis are known to be causedby bacteria. Principal forms implicated are Bacteroides gingivalis andActinobacillus actionmycetumcomitans. Gingivitis occurs from coronaldental plaque and periodontitis by the infection extending into theperiodontal pockets or spaced between the gingiva (gums) and the toothroot. Thus control of gingivitis is by reduction of microorganisms inthe coronal dental plaque and control of periodontitis by reduction ofpocket bacterial plaque in the gingival crevices as well as the saliva.

Clinical evidence has documented improvement in treatment of the abovediseases when stabilized chlorine dioxide is used. The organismscurrently implicated to the above are listed as follows:

1. Gingivitis

Actinomyces forms including Actinomyces

israeli

Coccus forms

2. Acute Necrotizing Ulcerative Gingivitis

Spirochetes

Bacteroides intermedius

Fusiform nucleatum

3. Juvenile Periodontitis

Actinobacillus actinomycetumcomitans

Capnocytophagia

Bacteroides intermedius

4. Adult periodontitis

Bacteroides gingivalis

Bacteroides intermidius

Actinobacillus actinomycetumcomitans

Vibrio nucleatum

Fusobactium nucleatum

Fusobactium bacteroides

Anerobic cocci

Research has demonstrated that stabilized chlorine dioxide is lethal toBacteriodes gingivalis and Actincbacillus actinomycetumcomitans in vitroat the 95% level in twenty seconds with a 0.02% concentration. Researchin vivo demonstrates that these organisms are significantly reduced oreliminated in humans when chlorine dioxide agent is applied to thepocket area using a syringe or water injection device with a needle toforce penetration into the gingival crevices with the chlorine dioxideconcentration in the range of 0.05% to 0.2%. Both gingivitis andperiodontitis cause an increase in the rate of epithelial cellssloughing aggrevating oral malodor and causing some ulceration of tissueleaving the gingival bleeding which is also reduced by treatment with asolution of stabilized chlorine dioxide.

Chlorine dioxide is thus highly useful in the treatment of gingivitis,periodontitis in its various forms and bleeding gingiva.

EXAMPLE V Denture Soak

The malodors of the mouth result substantially from the volatile sulfurcompounds which are present in saliva. Saliva coats and penetratesdental prosthetic devices including full dentures and partial dentures.Further, food and other cellular debris adheres to dental prostheses.Bacteria accumulates on and in the microscopic faults and pores of theseprosthetic devices. Chlorine dioxide has been demonstrated as abactericide and disinfectant and is effective for neutralizingsulfur-based malodors, removing organic debris from dental prosthesisand as a disinfectant and bactericide. As a dental soak the solution isantimicrobial, removes sulfur compounds and breaks down organic materialand can be used in solution form having a concentration of fromapproximately 0.002% to 0.27%.

EXAMPLE VI Cellular Debridement Agent

Many wounds and desquamative diseases such as Lichen Planus,Desquamative Gingivitis and desquamative dermatological disease areaided by organic debridement agents and antibicrobial agents. Solutionor composition containing chlorine dioxide in 0.05% to 0.1% and higherconcentrations is effective to treat these problems. One particularapplication would be in veterinarian applications for the purpose ofreducing odor attendant to these wounds and diseases.

EXAMPLE VII Sanitizer and Cold Sterilization Agent

The known bacterial, fungicidal and viralcidal characteristics ofchlorine dioxide also make it extremely useful as a sanitizer which canbe a solution in which materials can be dipped or by application in anaerosol spray. The sanitizer can be used for food, sickroom use,bathroom and cold sterilization of many instruments and pieces ofequipment are generally not amenable to autoclave sterilization. Again,the concentration of the sanitizing or sterilization agent wouldpreferably be in the range of from 0.005% to 2.0%.

EXAMPLE VIII Contact Lens Soak

Contact lenses accumulate bacteria and cellular debris from the eye. Theknown bactericidal, fungicidal and viraloidal capacity of chlorinedioxide along with the low toxicity makes chlorine dioxide solution anideal lens soak. In addition, capacity to degrade organic debris keepsthe lens clean and nonirritating. The preferred range of concentrationis 0.005% to 0.2% in sterilized water.

It will be seen from the foregoing that chlorine dioxide in solution oras part of a composition or compound is effective in treating andpreventing the formation of mouth malodor, as a suitable chemical plaquecontrol agent, and as a bactericide, viralcide and fungicide superior toother compositions used today. Chlorine dioxide has been used for manyyears in other areas and extensive study in animals and in man havedemonstrated its low toxicity and safety. Chlorine dioxide is approvedby the Environmental Protection Agency (EPA Reg. No. 9048-3) for waterpurification, food preparation and preservation as well as abacteriostatic, fungistatic and viralstatic agent.

It will be obvious that various changes, alterations and modificationsto the method and process described herein may be made. To the extentthat such changes, alterations and modifications do not depart from thespirit and scope of the appended claims, they are intended to beemcompassed therein.

I claim:
 1. A method for reducing dental plaque, said method comprisingthe step of retarding degradation of sucrose into glucose or fructose bykilling and by reducing the number of Streptococcus mutans to a morethan 90% level through topical application within the oral cavity for aperiod of ten seconds of a solution of stabilized chlorine dioxide inthe form of a paste and of a concentration in the range of 0.005% to0.2%.
 2. The method as set forth in claim 1 including the step ofpolishing the teeth through employment of clay as the paste.
 3. Themethod as set forth in claim 1 wherein the paste comprises a clay andwherein the solution of chlorine dioxide has been absorbed in the clay.